A continuation of our studies on the regulation of cholesterol, bile acid and serum lipoprotein synthesis in mammalian liver is proposed. In these studies we will attempt to determine whether insulin, triiodothyronine, glucagon, hydrocortisone, cholesterol and cholestyramine regulate beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase activity by changing the rates of enzyme synthesis or degradation, or by changing the activity of pre-existing enzyme. Other studies with this enzyme will be directed toward a determination of the presence or absence of enzymatically inactive HMG-CoA reductase in liver under certain dietary or hormonal states. They will also be directed towards attempts to determine whether allosteric regulators of HMG-CoA reductase activity exist. Studies with cholesterol-7alpha-hydroxylase, the rate-limiting enzyme of bile acid synthesis, will concentrate primarily on attempts to purify this enzyme to homogeneity. Those on serum lipoproteins will be concerned with the purification of apolipoproteins to homogeneity, the preparation of antisera to each and the identification of factors that affect the rates of synthesis of these apoproteins in primary liver cell cultures. BIBLIOGRAPHIC REFERENCES: Lakshmanan, M.R., Nepokroeff, C.M., Kim, M., and Porter, J.W. (1975) Arch. Biochem. Biophys. 169, 737-745. Adaptive synthesis of fatty acid synthetase and acetyl-CoA carboxylase by isolated rat liver cells. Nepokroeff, C.M., Qureshi, A.A., and Porter, J.W. (1975) Biochem. Biophys. Res. Commun. 67, 345-352. Cell-free synthesis of pigeon liver fatty acid synthetase.